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Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age

Hanson, Ellen ; Nilsson, Staffan ; Jood, Katarina ; Norrving, Bo LU ; Engström, Gunnar LU ; Blomstrand, Christian ; Lindgren, Arne LU ; Melander, Olle LU orcid and Jern, Christina (2013) In PLoS ONE 8(9).
Abstract
Background and Purpose: Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. Methods: The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmo Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years).... (More)
Background and Purpose: Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. Methods: The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmo Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. Results: The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample <= 70 years. Conclusions: We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
9
article number
e75286
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000325218700069
  • scopus:84884550124
  • pmid:24086496
ISSN
1932-6203
DOI
10.1371/journal.pone.0075286
language
English
LU publication?
yes
id
b30b6e22-63f0-425e-a289-9c99ba209e27 (old id 4212326)
date added to LUP
2016-04-01 14:34:39
date last changed
2024-01-10 05:40:14
@article{b30b6e22-63f0-425e-a289-9c99ba209e27,
  abstract     = {{Background and Purpose: Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. Methods: The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmo Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. Results: The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample &lt;= 70 years. Conclusions: We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.}},
  author       = {{Hanson, Ellen and Nilsson, Staffan and Jood, Katarina and Norrving, Bo and Engström, Gunnar and Blomstrand, Christian and Lindgren, Arne and Melander, Olle and Jern, Christina}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age}},
  url          = {{https://lup.lub.lu.se/search/files/4046241/4359160}},
  doi          = {{10.1371/journal.pone.0075286}},
  volume       = {{8}},
  year         = {{2013}},
}